Insights in the glycosylation steps during biosynthesis of the antitumor anthracycline cosmomycin: Characterization of two glycosyltransferase genes

Leandro M. Garrido; Felipe Lombó; Irfan Baig; Mohammad Nur-E-Alam; Renata L.A. Furlan; Charlotte C. Borda; Alfredo Braña; Carmen Méndez; José A. Salas; Jürgen Rohr; Gabriel Padilla

doi:10.1007/s00253-006-0453-z

Insights in the glycosylation steps during biosynthesis of the antitumor anthracycline cosmomycin: Characterization of two glycosyltransferase genes

Leandro M. Garrido, Felipe Lombó, Irfan Baig, Mohammad Nur-E-Alam, Renata L.A. Furlan, Charlotte C. Borda, Alfredo Braña, Carmen Méndez, José A. Salas, Jürgen Rohr, Gabriel Padilla

Pharmaceutical Sciences

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25 Scopus citations

Abstract

Glycosylation pattern in cosmomycins is a distinctive feature among anthracyclines. These antitumor compounds possess two trisaccharide chains attached at C-7 and C-10, each of them with structural variability, mainly at the distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis. Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated with the generation of five new derivatives. Structural elucidation of these compounds showed altered glycosylation patterns indicating the capability of both glycosyltransferases of transferring deoxysugars to both sides of the aglycone and the flexibility of CosK with respect to the deoxysugar donor. A model is proposed for the glycosylation steps during cosmomycins biosynthesis.

Original language	English
Pages (from-to)	122-131
Number of pages	10
Journal	Applied Microbiology and Biotechnology
Volume	73
Issue number	1
DOIs	https://doi.org/10.1007/s00253-006-0453-z
State	Published - Nov 2006

Bibliographical note

Funding Information:
Acknowledgements The authors thank specially collaborations of Drs. Arthur Gruber, Alda Madeira, Gilson P. Manfio, Valéria M. de Oliveira, and Hernando Del Portillo for the sequencing of the DNA, and the technical support of Dr. Fabiana Fantinatti-Garboggini, Dr. Emilio Fernando Merino, Karen Christina M. Simioni, and Daniele B. de Souza. This work was supported by grants from FAPESP to L.M.G. (00/07288-0) and to G.P. (03/00135-1), from the Spanish Ministry of Education and Science to L.M.G, R.L.A.F and C.M. (BMC2002-03599), and from the US National Institutes of Health (CA 091901 and CA 102102) to J.R. We thank Obra Social Cajastur for financial support to F.L.

Funding

Acknowledgements The authors thank specially collaborations of Drs. Arthur Gruber, Alda Madeira, Gilson P. Manfio, Valéria M. de Oliveira, and Hernando Del Portillo for the sequencing of the DNA, and the technical support of Dr. Fabiana Fantinatti-Garboggini, Dr. Emilio Fernando Merino, Karen Christina M. Simioni, and Daniele B. de Souza. This work was supported by grants from FAPESP to L.M.G. (00/07288-0) and to G.P. (03/00135-1), from the Spanish Ministry of Education and Science to L.M.G, R.L.A.F and C.M. (BMC2002-03599), and from the US National Institutes of Health (CA 091901 and CA 102102) to J.R. We thank Obra Social Cajastur for financial support to F.L.

Funders	Funder number
Obra Social Cajastur
National Institutes of Health (NIH)	CA 102102
National Childhood Cancer Registry – National Cancer Institute	R01CA091901
Fundação de Amparo à Pesquisa do Estado de São Paulo	03/00135-1, 00/07288-0
Ministerio de Educación, Cultura y Deporte	BMC2002-03599

ASJC Scopus subject areas

Biotechnology
Applied Microbiology and Biotechnology

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Garrido, L. M., Lombó, F., Baig, I., Nur-E-Alam, M., Furlan, R. L. A., Borda, C. C., Braña, A., Méndez, C., Salas, J. A., Rohr, J., & Padilla, G. (2006). Insights in the glycosylation steps during biosynthesis of the antitumor anthracycline cosmomycin: Characterization of two glycosyltransferase genes. Applied Microbiology and Biotechnology, 73(1), 122-131. https://doi.org/10.1007/s00253-006-0453-z

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title = "Insights in the glycosylation steps during biosynthesis of the antitumor anthracycline cosmomycin: Characterization of two glycosyltransferase genes",

abstract = "Glycosylation pattern in cosmomycins is a distinctive feature among anthracyclines. These antitumor compounds possess two trisaccharide chains attached at C-7 and C-10, each of them with structural variability, mainly at the distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis. Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated with the generation of five new derivatives. Structural elucidation of these compounds showed altered glycosylation patterns indicating the capability of both glycosyltransferases of transferring deoxysugars to both sides of the aglycone and the flexibility of CosK with respect to the deoxysugar donor. A model is proposed for the glycosylation steps during cosmomycins biosynthesis.",

author = "Garrido, {Leandro M.} and Felipe Lomb{\'o} and Irfan Baig and Mohammad Nur-E-Alam and Furlan, {Renata L.A.} and Borda, {Charlotte C.} and Alfredo Bra{\~n}a and Carmen M{\'e}ndez and Salas, {Jos{\'e} A.} and J{\"u}rgen Rohr and Gabriel Padilla",

note = "Funding Information: Acknowledgements The authors thank specially collaborations of Drs. Arthur Gruber, Alda Madeira, Gilson P. Manfio, Val{\'e}ria M. de Oliveira, and Hernando Del Portillo for the sequencing of the DNA, and the technical support of Dr. Fabiana Fantinatti-Garboggini, Dr. Emilio Fernando Merino, Karen Christina M. Simioni, and Daniele B. de Souza. This work was supported by grants from FAPESP to L.M.G. (00/07288-0) and to G.P. (03/00135-1), from the Spanish Ministry of Education and Science to L.M.G, R.L.A.F and C.M. (BMC2002-03599), and from the US National Institutes of Health (CA 091901 and CA 102102) to J.R. We thank Obra Social Cajastur for financial support to F.L.",

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Garrido, LM, Lombó, F, Baig, I, Nur-E-Alam, M, Furlan, RLA, Borda, CC, Braña, A, Méndez, C, Salas, JA, Rohr, J & Padilla, G 2006, 'Insights in the glycosylation steps during biosynthesis of the antitumor anthracycline cosmomycin: Characterization of two glycosyltransferase genes', Applied Microbiology and Biotechnology, vol. 73, no. 1, pp. 122-131. https://doi.org/10.1007/s00253-006-0453-z

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AU - Lombó, Felipe

AU - Baig, Irfan

AU - Nur-E-Alam, Mohammad

AU - Furlan, Renata L.A.

AU - Borda, Charlotte C.

AU - Braña, Alfredo

AU - Méndez, Carmen

AU - Salas, José A.

AU - Rohr, Jürgen

AU - Padilla, Gabriel

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N2 - Glycosylation pattern in cosmomycins is a distinctive feature among anthracyclines. These antitumor compounds possess two trisaccharide chains attached at C-7 and C-10, each of them with structural variability, mainly at the distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis. Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated with the generation of five new derivatives. Structural elucidation of these compounds showed altered glycosylation patterns indicating the capability of both glycosyltransferases of transferring deoxysugars to both sides of the aglycone and the flexibility of CosK with respect to the deoxysugar donor. A model is proposed for the glycosylation steps during cosmomycins biosynthesis.

AB - Glycosylation pattern in cosmomycins is a distinctive feature among anthracyclines. These antitumor compounds possess two trisaccharide chains attached at C-7 and C-10, each of them with structural variability, mainly at the distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis. Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated with the generation of five new derivatives. Structural elucidation of these compounds showed altered glycosylation patterns indicating the capability of both glycosyltransferases of transferring deoxysugars to both sides of the aglycone and the flexibility of CosK with respect to the deoxysugar donor. A model is proposed for the glycosylation steps during cosmomycins biosynthesis.

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Insights in the glycosylation steps during biosynthesis of the antitumor anthracycline cosmomycin: Characterization of two glycosyltransferase genes

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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